Fast and simple detection methods for the 4-base pair deletion of canine MDR1/ABCB1 gene by PCR and isothermal amplification

Dogs with a 4-bp deletion in the MDR1 (or ABCB1) gene show intolerance to certain drugs routinely used in veterinary medicine, such as ivermectin, vincristine, and doxorubicin. The mutation leads to a dysfunctional P-glycoprotein drug transporter, which results in drug accumulation in the brain and severe neurotoxicity. A rapid and accurate in-house test to determine the genotype of patients in cases of acute neurotoxic signs or in tumor patients is desirable. We describe a cost-effective detection method with simple technical equipment for veterinary practice. Two allele-specific methods are presented, which allow discrimination of all genotypes, require little hands-on time, and show the results within similar to 1 h after DNA sampling. DNA from buccal swabs of 115 dogs with known genotype (no mutation, n = 54;heterozygous for the mutation, n = 37;homozygous for the mutation, n = 24) was extracted either by using a column-based extraction kit or by heating swabs in a simple NaOH-Tris buffer. Amplification was performed either by allele-specific fast polymerase chain reaction or by allele-specific loop-mediated isothermal amplification (LAMP). Analysis was done either on agarose gels, by simple endpoint visualization using ultraviolet light, or by measuring the increase of fluorescence and time to threshold crossing. Commercial master mixes reduced the preparation time and minimized sources of error in both methods. Both methods allowed the discrimination of all 3 genotypes, and the results of the new methods matched the results of the previous genotyping. The presented methods could be used for fast individual MDR1/ABCB1 genotyping with less equipment than existing methods

Wenn Engländer nach Ungarn reisen ...

Bei der vorliegenden Arbeit handelt es sich um einen imagologischen Vergleich englischer Reiseberichte über Ungarn im 17., 18. und 19. Jahrhundert. Sie behandelt Reiseberichte über Ungarn aus der Feder der englischen Reisenden Edward Brown, Robert Townson, Richard Bright und John Paget. Um die Reiseberichte historisch einzuordnen, gebe ich im Kapitel 5 einen Überblick über die politische und wirtschaftliche Situation Ungarns, angefangen bei der Schlacht von Mohács im Jahre 1556, über die Dreiteilung des Landes und die 150 Jahre andauernde Türkenherrschaft, die Aufstände der Kurruzzen, die Zeit von Maria Theresia und Joseph II. bis hin zur Revolution von 1848 und dem österreichisch-ungarischen Ausgleich im Jahre 1867. Auch mit der Frage nach der literarischen Gattung eines Reiseberichtes setze ich mich in dieser Arbeit auseinander, denn diese Frage ist bis heute noch nicht restlos beantwortet. Die Herausarbeitung der interkulturellen Begegnungen zwischen Engländern und Ungarn spielt in dieser Arbeit eine wichtige Rolle. Im vierten Kapitel dieser Arbeit gehe ich auf die vor allem im 18. Jahrhundert allgemein bekannten Fremdbilder von anderen Kulturen sowie auf den Unterschied von Auto- und Heterostereotyp ein. Hierbei lege ich ein besonderes Augenmerk auf die aus der ersten Hälfte des 18. Jahrhunderts stammende Völkertafel, ein Ölgemälde, dass diverse europäische Völker in ihrer Nationaltracht darstellt und sie in Hinblick auf die verschiedenen Bereiche des Lebens sowie auf das Land, in dem sie leben, charakterisiert. Von Interesse waren für mich in erster Linie die Charakterisierungen der „Engerländer“ sowie der „Ungern“, die ich miteinander vergleiche. Im Laufe ihrer Reisen waren die Reisenden neben Problemen des Vorankommens auch mit sprachlichen Barrieren konfrontiert. Im damaligen Ungarn war Ungarisch bei Weitem nicht die einzige Barriere denn es lebten in Ungarn neben Ungarn unter anderen auch Deutsche, Slovaken, Slavonier, Kroaten, Walachen und Russen, die keinesfalls nur weil sie in Ungarn lebten, auch der ungarischen Sprache mächtig waren. Auch darauf gehe ich in dieser Arbeit ein

Von der Gebärde zur Aufzeichnung

Die vorliegende Masterarbeit spannt den Bogen ausgehend von der Terminologiewissenschaft über die Gebärdensprachlexikographie zum Gebärdensprachdolmetschen und zurück. Wie können GebärdensprachdolmetscherInnen ihre Terminologie verwalten? Ausgehend von dieser Fragestellung wird eine Auswahl unterschiedlicher internationaler Ansätze präsentiert. Die ersten beiden Kapitel verstehen sich als einführende Kapitel in die Thematiken Gebärdensprachen und Gehörlosigkeit. Kapitel eins fasst den internationalen Forschungsstand über Gebärdensprachen zusammen und geht auf die Österreichische Gebärdensprache ein. In Kapitel zwei erfolgt eine Abgrenzung zwischen taubstumm / taub / gehörlos / gebärdensprachig. Weiters wird die Bildungssituation von Gehörlosen in Österreich erörtert sowie die Bedeutung von Gehörlosengemeinschaften hervorgehoben. Kapitel drei gibt einen Einblick in das Gebärdendolmetschen. Nach einem kurzen historischen Überblick werden die Einsatzbereiche von GebärdensprachdolmetscherInnen beleuchtet und Gebärdensprach-Dolmetschtechniken zusammengefasst. In Kapitel vier werden Grundlagen der Terminologiewissenschaft präsentiert. Dabei wird unter anderem auf die Abgrenzung zwischen Begriff / Benennung / Gegenstand / Terminus sowie auf den Beruf des/der TerminologIn eingegangen. Kapitel fünf widmet sich der angewandten Terminologiearbeit. Die Funktionen und Bedeutungen terminologischer Systeme werden erläutert und Modelle von Martin Will, Wladimir Kutz, Anja Rütten und Heidrun Gerzymisch-Arbogast präsentiert. Der Hauptfokus liegt dabei auf der Dolmetschorientierten Terminologiearbeit nach Martin Will. Kapitel sechs widmet sich der Gebärdensprachlexikographie. Nach einem geschichtlichen Überblick, in dem die Arbeiten von Abbée de l’Epée, Pierre Desloges, Friedrich Stork und Romedius Knoll erörtert werden, werden derzeitige österreichische Bemühungen und Projekte mit dem Ziel gebärdensprachlicher Aufzeichnungen beschrieben. Danach folgt ein Überblick über internationale Gebärdenschriften wie beispielsweise jene von Valerie Sutton sowie das Hamburger Notationssystem HamNoSys und weitere Projekte wie H.A.N.D.S. oder syncWRITER. Zum Abschluss der Thematik werden Datenhandschuh- und Motion Capture-Technologien angesprochen.This Master‘s thesis focuses on sign language interpreting on the one hand and terminology on the other hand and tries to point out the link between terminology and interpreting. The first two chapters are to be understood as orientation and introduction in the topics sign languages and deafness. Chapter one presents sign language universals summarizing the international state of the art with little focus on the Austrian Sign Language. Chapter two deals with deafness and hearing impairments and explains the difference between deaf and Deaf as well as the importance and role of Deaf communities in Austria and all over the world. Chapter three provides an insight in sign language interpreting. After a short historic overview the working fields of sign language interpreters as well as interpreting techniques are presented. In chapter four an overview about the discipline of terminology work is given defining the difference between terms, concepts and denominations and focusing on the profession of a terminologist. After this introduction to terminology chapter five deals with applied terminology and discusses the functions and importance of terminological systems. This chapter mainly focuses on the interpreter-oriented terminology work of Martin Will. Besides, it presents the models of Wladimir Kutz, Anja Rütten and Heidrun Gerzymisch-Arbogast. Chapter six focuses on sign language lexicography. After a historic overview presenting the work of Abbé de l’Epée, Pierre Desloges, Friedrich Stork and Romedius Knoll, Austrian terminology projects dealing with Austrian Sign Language are presented. Following that, an overview is given about international sign writing systems including the work of Valerie Sutton, the Hamburg Notation System for Sign Languages HamNoSys, as well as the projects H.A.N.D.S., syncWRITER and some more. In order to complete the topic, data glove and motion capture technologies are shortly presented

A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment

Increasing evidence suggests that specific physiological measures may serve as biomarkers for successful treatment to alleviate symptoms of pathological anxiety. Studies of autonomic function investigating parameters such as heart rate (HR), HR variability and blood pressure (BP) indicated that HR variability is consistently reduced in anxious patients, whereas HR and BP data show inconsistent results. Therefore, HR and HR variability were measured under various emotionally challenging conditions in a mouse model of high innate anxiety (high anxiety behaviour; HAB) vs. control normal anxiety-like behaviour (NAB) mice. Baseline HR, HR variability and activity did not differ between mouse lines. However, after cued Pavlovian fear conditioning, both elevated tachycardia and increased fear responses were observed in HAB mice compared to NAB mice upon re-exposure to the conditioning stimulus serving as the emotional stressor. When retention of conditioned fear was tested in the home cage, HAB mice again displayed higher fear responses than NAB mice, while the HR responses were similar. Conversely, in both experimental settings HAB mice consistently exhibited reduced HR variability. Repeated administration of the anxiolytic NK1 receptor antagonist L-822429 lowered the conditioned fear response and shifted HR dynamics in HAB mice to a more regular pattern, similar to that in NAB mice. Additional receiver-operating characteristic (ROC) analysis demonstrated the high specificity and sensitivity of HR variability to distinguish between normal and high anxiety trait. These findings indicate that assessment of autonomic response in addition to freezing might be a useful indicator of the efficacy of novel anxiolytic treatments

Editorial: Home Cage-Based Phenotyping in Rodents: Innovation, Standardization, Reproducibility and Translational Improvement

Peer Reviewe

Seizures and disturbed brain potassium dynamics in the leukodystrophy megalencephalic leukoencephalopathy with subcortical cysts

OBJECTIVE: Loss of function of the astrocyte-specific protein MLC1 leads to the childhood-onset leukodystrophy "megalencephalic leukoencephalopathy with subcortical cysts" (MLC). Studies on isolated cells show a role for MLC1 in astrocyte volume regulation and suggest that disturbed brain ion and water homeostasis is central to the disease. Excitability of neuronal networks is particularly sensitive to ion and water homeostasis. In line with this, reports of seizures and epilepsy in MLC patients exist. However, systematic assessment and mechanistic understanding of seizures in MLC are lacking. METHODS: We analyzed an MLC patient inventory to study occurrence of seizures in MLC. We used two distinct genetic mouse models of MLC to further study epileptiform activity and seizure threshold through wireless extracellular field potential recordings. Whole-cell patch-clamp recordings and K+-sensitive electrode recordings in mouse brain slices were used to explore the underlying mechanisms of epilepsy in MLC. RESULTS: An early onset of seizures is common in MLC. Similarly, in MLC mice, we uncovered spontaneous epileptiform brain activity and a lowered threshold for induced seizures. At the cellular level, we found that although passive and active properties of individual pyramidal neurons are unchanged, extracellular K+dynamics and neuronal network activity are abnormal in MLC mice. INTERPRETATION: Disturbed astrocyte regulation of ion and water homeostasis in MLC causes hyperexcitability of neuronal networks and seizures. These findings suggest a role for defective astrocyte volume regulation in epilepsy. Ann Neurol 2018;83:636-649

Daily torpor: When heart and brain go cold - Nonlinear cardiac dynamics in the seasonal heterothermic Djungarian hamster

Djungarian hamsters (Phodopus sungorus) acclimated to short photoperiod display episodes of spontaneous daily torpor with metabolic rate depressed by ∼70%, body temperature (

Overexpression of 5-HT2C receptors in forebrain leads to elevated anxiety and hypoactivity

The 5-HT2C receptor has been implicated in mood and eating disorders. In general, it is accepted that 5-HT2C receptor agonists increase anxiety behaviours and induce hypophagia. However, pharmacological analysis of the roles of these receptors is hampered by the lack of selective ligands and the complex regulation of receptor isoforms and expression levels. Therefore, the exact role of 5-HT2C receptors in mood disorders remain controversial, some suggesting agonists and others suggesting antagonists may be efficacious antidepressants, while there is general agreement that antagonists are beneficial anxiolytics. In order to test the hypothesis that increased 5-HT2C receptor expression, and thus increased 5-HT2C receptor signalling, is causative in mood disorders, we have undertaken a transgenic approach, directly altering the 5-HT2C receptor number in the forebrain and evaluating the consequences on behaviour. Transgenic mice overexpressing 5-HT2C receptors under the control of the CaMKIIα promoter (C2CR mice) have elevated 5-HT2C receptor mRNA levels in cerebral cortex and limbic areas (including the hippocampus and amygdala), but normal levels in the hypothalamus, resulting in > 100% increase in the number of 5-HT2C ligand binding sites in the forebrain. The C2CR mice show increased anxiety-like behaviour in the elevated plus-maze, decreased wheel-running behaviour and reduced activity in a novel environment. These behaviours were observed in the C2CR mice without stimulation by exogenous ligands. Our findings support a role for 5-HT2C receptor signalling in anxiety disorders. The C2CR mouse model offers a novel and effective approach for studying disorders associated with 5-HT2C receptors

Sound Signalling in Orthoptera

The sounds produced by orthopteran insects are very diverse. They are widely studied for the insight they give into acoustic behaviour and the biophysical aspects of sound production and hearing, as well as the transduction of sound to neural signals in the ear and the subsequent processing of information in the central nervous system. The study of sound signalling is a multidisciplinary area of research, with a strong physiological contribution. This review considers recent research in physiology and the links with related areas of acoustic work on the Orthoptera